Expression of factors involved in regulation of DNA mismatch repair- and apoptosis pathways in ovarian cancer patients

Abstract

A major obstacle in treatment of ovarian cancer is intrinsic or acquired drug resistance causing failure of chemotherapy followed by a poor clinical outcome. Drug resistance of ovarian carcinoma can be caused by dysregulation of cellular factors involved in regulation of apoptosis and DNA repair pathways. In this study, 73 ovarian carcinoma specimens obtained before and after chemotherapy were analysed by immunohistochemistry for expression of seven proteins playing an important role in regulation of DNA mismatch repair and apoptosis. The prognostic significance of these proteins in the meaning of overall and progression-free survival was evaluated in univariate and multivariate analysis. Bcl-x L , hMSH2, caspase-3, p21 and p53 displayed prognostic importance in univariate analysis. Furthermore, it was demonstrated that caspase-3 and p21 were also independent prognostic markers for both, overall and progression-free survival. In conclusion, these data indicate that analysis of proteins involved in DNA mismatch repair and apoptosis can be useful for prediction of clinical outcome in ovarian carcinoma patients.

Serum and tissue biomarkers as predictive and prognostic variables in epithelial ovarian cancer

“…p21 expression has been detected in 16-74% of EOCs, but its predictive and prognostic relevance is still uncertain [84,94,104,[125][126][127][128][129][130][131][132][133][134][135] (Table 4(a)). In a study on 204 patients who received with platinum-based chemotherapy, high-p21 expression was an independent positive predictor of platinum-sensitive response, defined as complete response with disease-free survival longer than 6 months [130].…”

Genomic instability in breast and ovarian cancers: translation into clinical predictive biomarkers

“…Consequently, multiple studies investigated MMR deficiency in breast and ovarian cancer (via IHC, methylation, or microsatellite instability detection) in relation to response or outcome after chemotherapy [172,[190][191][192][193][194][195][196][197]. These studies reached opposing conclusions based on associations of low MMR gene expression with both clinical progressive disease (e.g., [191]) and longer OS (e.g., [197]).…”

“…Consequently, multiple studies investigated MMR deficiency in breast and ovarian cancer (via IHC, methylation, or microsatellite instability detection) in relation to response or outcome after chemotherapy [172,[190][191][192][193][194][195][196][197]. These studies reached opposing conclusions based on associations of low MMR gene expression with both clinical progressive disease (e.g., [191]) and longer OS (e.g., [197]). The reason for these contradictory results is that the quality of all studies was compromised by analysis of small subgroups within heterogeneous patient populations (for example varying chemotherapy regimens within studies [190,195]), risk of unnoticed associations with other potential prognostic patient characteristics, or studying only clinical responses (e.g., [196]; for details regarding the above-mentioned studies, see Supplementary Table 1).…”

Downregulation of transient receptor potential cation channel, subfamily C, member 1 contributes to drug resistance and high histological grade in ovarian cancer

“…3). Among those, CDKN1A (43,44), FOS (45,46), WWOX (47) and VMP1 (48) are associated with drug resistance in OC. Collectively, among the 21 proteins/genes found to interact with TRPC1, 14 were associated with drug resistance in OC.…”